WO2014024205A1

WO2014024205A1 - A method for preparing (s)-(+)-n, n-dimethyl-3-(naphthalen-1-yloxy)-1-phenylpropan-1-amine or its salt and intermediate thereof

Info

Publication number: WO2014024205A1
Application number: PCT/IN2013/000134
Authority: WO
Inventors: Rakesh SAHAY; Syed Mudassar Ajaz HUSSAIN; Anjan ROY
Original assignee: R L Fine Chem
Priority date: 2012-08-07
Filing date: 2013-03-05
Publication date: 2014-02-13

Abstract

The present invention is in relation to a method for preparation of (S)-(+)-N, N-dimethyl-[3-(naphthalen-1-yloxy)-1-phenylpropyl]amine or its pharmaceutically acceptable salt and intermediate thereof. The method is industrially viable, economical, eco-friendly and helps in obtaining the target compound in short time with high enantiomeric purity.

Description

A METHOD FOR PREPARING S (+)-N, N-DIMETHYL-3- (NAPHTHALEN- 1 -YLOX Y)- 1-PHENYLPROPAN-l - AMINE OR ITS SALT

AND INTERMEDIATE THEREOF

TECHNICAL FIELD The present invention is in relation to a method for preparation of f¾)-(+)-N,iV-dimethyl-[3- (naphthalen-l -yloxy)-l-phenylpropyl]amine commonly known as Dapoxetine and its pharmaceutically acceptable salt from3-(Naphmalene-l -yloxy)-l-phenylpropan-l -ol and intermediate thereof. The said method is simple, industrially viable, economical,eco-friendly and helps in obtaining the target compound in short time with high enantiomeric purity.

BACKGROUND

The serotonin reuptake inhibitor (SSRIs) are used in the treatment of depression, anxiety disorders and personality disorders. 5|)-(+)-NN-dimethyl-[3-(naphthalen-l-yloxy)-l - phenylpropyl] amine known as Dapoxetine is a potential SSRI often used to manage male sexual disorder, primarily to manage premature ejaculation(PE).

Dapoxetine is a short acting SSRI and hence is suited for managing premature ejaculation. It is reported through preclinical models that Dapoxetine significantly inhibit ejaculatory expulsion reflexes, acting at a supraspinal level.

Fig-I:Dapoxetine

l Dapoxetine, with a chiral center as represented by figure 1, is present in enantiomeric forms. The (¾)-(+)-Dapoxetine being the eutomer for managing premature ejaculation. Many methods are described in the literature for the preparation of Dapoxetine since its disclosure through US Patent No.5,135,947 by Eli Lilly.

US Patent No. 5,135,947 provides a method for preparation of Dapoxetine and other l-phenyl-3- naphthalenyloxypropanamines. In yet another US Patent from Eli Lilly, US5, 292,962, a method of preparation of Dapoxetine enantiomers has been described. WO2008/035358describes a multistep preparation of (+)-- Dapoxetine starting from Benzene and chloropropionyl chloride under Friedel-Crafts reaction.

Soyeong Kang et al in JOC, 2010,75,237-40 gives a method for the preparation of enantioselctive synthesis of Dapoxetine from 3-phenyl-l-propanol. The present invention is focussed to alleviate the drawbacks of the methods known in the art for the preparation of Dapoxetine. Accordingly the present invention provides a method wherein simple reagents are used, minimum workup steps are involved thereby reducing the effluents produced during the preparation. The process through the novel intermediate also helps in reducing the production of effluent inorganic salts. This renders the method eco-friendly, the basic tenet of any industrial production. The Dapoxetine produced is also enantiomerically pure.

STATEMENT OF INVENTION

Accordingly, the present invention provides a method for preparing (S)-(+)~N, N-Dimethyl-3- (Naphthalen-l-yloxy)-l-phenylpropan-l -amine or its pharmaceutically acceptable salt, said method comprising acts of, preparing compound of formula I from 3 -(Naphthalene- l-yloxy)-l- phenylpropane- 1 -ol,

Wherein X= CI or Br

Formula I

preparing CS -(+)-N,N-Dimethyl-3-(Naphthalen-l-yloxy)-l-phenylpropan-l -amine tartrate from the compound of formula I, reacting (S)- (+)-N,N-Dimethyl-3-(Naphthalen-l-yloxy)-l- phenylpropan-1 -amine, tartrate with base to obtain (S)- (+)-N,N-Dimethyl-3-(Naphthalen-l- yloxy)-l-phenylpropan-l -amine, and optionally converting f¾ -N,N-Dimethyl-3-(Naphthalen-l- yloxy)-l-phenylpropan-l -amine to its pharmaceutically acceptable salt; a compound of formula I;

Wherein X=C1 or Br

Formula I

a method for preparing compound of formula I, comprising act of reacting 3 -(Naphthalene- 1- yloxy)-l-phenylpropane-l-ol with halogenating agent; a method for preparing (S)- (+)-N, N- Dimethyl-3-(Naphthalen-l-yloxy)-l-phenylpropan-l -amine or its pharmaceutically acceptable salt from formula I, said method comprising acts of, converting the compound of formula I to (S)- (+)-N, N-Dimethyl-3-(Naphthalen-l-yloxy)-l-phenylpropan-l -amine tartrate; reacting the(S)- (+)-N,N-Dimethyl-3-(Naphthalen-l-yloxy)-l-phenylpropan-l -amine tartrate with base to obtain (S)- (+)-N,N-Dimethyl-3-(Naphthalen-l-yloxy)-l-phenylpropan-l -amine and optionally converting the fS^-N,N-Dimethyl-3-(Naphthalen-l-yloxy)-l-phenylpropan-l -amine to its pharmaceutically acceptable salt. DETAILED DESCRIPTION OF INVENTION

The present invention is in relation to a method for preparing (S)- (+)-N, N-Dimethyl-3- (Naphthalen-l-yloxy)-l-phenylpropan-l -amine or its pharmaceutically acceptable salt, said method comprising acts of a. preparing compound of formula I from 3-(Naphthalene-l-yloxy)-l-phenylpropane- l-ol;

Wherein X=C1 or Br

Formula I b. preparing \ e(S)- (+)-N, N-Dimethyl-3-(naphthalen-l-yloxy)-l-phenylpropan-l- amine tartrate from the compound of formula I ;

c. reacting the (S)- (+)-N,N-Dimethyl-3-(naphthalen-l-yloxy)-l-phenylpropan-l-amine tartrate with base to obtain the f¾)-N,N-Dimethyl-3-(naphthalen-l-yloxy)-l- phenylpropan-1 -amine; and

d. optionally converting the (S)- (+)-N,N-Dimethyl-3-(naphthalen-l-yloxy)-l- phenylpropan-1 -amine to its pharmaceutically acceptable salt.

In another embodiment of the present invention, the compound of formula I is prepared using halogenating reagent selected from a group comprising thionyl chloride, phosphorus trichloride, phosphorus pentachloride, zinc chloride in hydrochloric acid, thionyl bromide and mixture thereof.

In still another embodiment of the present invention, the N, N-Dimethyl-3 -(naphthalen-1 -yloxy)- 1-phenylpropan-l -amine tartrate is prepared by a method comprising acts of,

a. reacting the compound of formula I with dimethyl amine to obtain the N,N-Dimethyl-3- (Naphthalen-l-yloxy)-l-phenylpropan-l-amine; and b. treating the N,N-Dimethyl-3-(Naphthalen-l-yloxy)-l-phenylpropan-l -amine with tartaric acid to obtain the N, N-Dimethyl-3-(Naphthalen-l-yloxy)-l-phenylpropan-l -amine tartrate.

In still another embodiment of the present invention, wherein tartaric acid is selected from a group comprising L(+)-tartaric acid and D(-)-tartaric acid.

In yet another embodiment of the present invention, the base is selected from a group comprising sodium hydroxide, potassium hydroxide, potassium t- butoxide, strontium hydroxide, calcium hydroxide, barium hydroxide and mixture thereof.

In still another embodiment of the present invention, the (5^-N,N-Dimethyl-3-(Naphthalen-l- yloxy)-l-phenylpropan-l -amine is converted to its pharmaceutically acceptable salt using acid selected from a group comprising hydrochloric acid and hydrobromic acid

In another embodiment of the present invention, the pharmaceutically acceptable salt of (S)- N,N-Dimethyl-3 -(Naphthalen- 1 -yloxy)- 1 -phenylpropan- 1 -amine is salt of hydrochloric acid.

The present invention is also in relation to a compound of formula I,

Wherein X= CI or Br

Formula I

In another embodiment of the present invention, the compound of formula I is

The present invention is also in relation to a method for preparing compound of formula I, comprising act of reacting from 3 -(Naphthalene- l-yloxy)-l-phenylpropane-l-ol with halogenating agent.

In still another embodiment of the present invention, the halogenating agent is selected from a group comprising thionyl chloride, thionyl bromide, phosphorus trichloride, phosphorus pentachloride, zinc chloride in hydrochloric acid and mixture thereof.

In still another embodiment of the present invention, the halogenating agent is thionyl chloride.

In still another embodiment of the present invention, the reaction is carried out at a temperature ranging from about 0°C to about 10°C, preferably from about 0°C to about 5°C. The present invention is also in relation to a method for preparing (S)- (+)-N, N-Dimethyl-3- (naphthalen-l-yloxy)-l-phenylpropan-l -amine or its pharmaceutically acceptable salt from formula I, said method comprising acts of a. converting the compound of formula I to (S)- (+)-N, N-Dimethyl-3-(naphthalen-l- yloxy)- 1 -phenylpropan- 1 -amine tartrate;

Wherein X= CI or Br

Formula I

b. reacting ihe(S)- (+)-N,N-Dimethyl-3-(Naphthalen-l-yloxy)-l -phenylpropan- 1 -amine tartrate with base to obtain (S)- (+)- N,N-Dimethyl-3-(Naphthalen-l-yloxy)-l-phenylpropan-l- amine; and

c. optionally converting the (S)- (+)-N,N-Dimethyl-3-(Naphthalen-l-yloxy)-l- phenylpropan-1 -amine to its pharmaceutically acceptable salt.

The present invention deals with synthesis of N,N-Dimethyl-3-(naphthalen-l-yloxy)-l- phenylpropan-1 -amine, in particular (S)- (+)- N,N-Dimethyl-3-(naphthalen-l-yloxy)-l- phenylpropan-1 -amine its pharmaceutically acceptable salt with high enantiomeric and chemical purity using l -(3-Chloro-3 -phenylpropoxy) Naphthalene . The pharmaceutically acceptable salt of N, N-Dimethyl-3-(naphthalen-l-yloxy)-l- phenylpropan-1 -amine refers to the salt of hydrochloric acid or hydrobromic acid.

The presence of chiral center in the target molecule necessitate to adapt a method wherein the eutomer, (S)- (+)-N,N-Dimethyl-3-(Naphthalen-l-yloxy)-l-Phenylpropan-l -Amine is prepared with high eudismic ratio. The present invention helps in achieving the same by the usage of chiral acid, tartaric acid. The tartaric acid for optical resolution can be either D-(-)-Tartaric acid or L(+)-Tartaric acid.

The process of the present invention is also industrially viable because of the usage of simple reagents. The effluents and inorganic salts are minimum owing to the nature of the intermediate in the reaction. Thus the present invention provides an environmentally compatible reaction.

The process of the present invention is represented schematically by scheme- 1.

Accordingly, 3 -(naphthalene- l-yloxy)-l-phenylpropan-l-ol, is reacted with a halogenating reagent, preferably thionyl chloride to obtain a novel compound, l-(3-Chloro-3-phenylpropoxy)- naphthalene as intermediate. The l-(3-Chloro-3-phenylpropoxy)-naphthalene is further reacted with N, N-Dimethyl amine in triethyl amine to obtain the N,N-Dimethyl-3-(Naphthalen-l- yloxy)-l-phenylpropan-l -amine, the racemic target compound,N,N-Dimethyl-3-(Naphthalen-l- yloxy)-l-phenylpropan-l -amine is treated preferably and advantageously with chiral tartaric acid, preferably D(-)-tartaric acid to obtain the tartrate salt of the eutomer of N,N-Dimethyl-3- (Naphthalen-l-yloxy)-l-phenylpropan-l-aminein a single pot synthesis. The tartrate salt of Dapoxetine is treated with a base to obtain (S)- (+)-N,N-Dimethyl-3-(Naphthalen-l-yloxy)-l- phenylpropan- 1 -amine.

The (S)- (+)-N, N-Dimethyl-3-(naphthalen-l-yloxy)-l-phenylpropan-l -amine tartrate is of purity ranging from about 85% to about 95% and (R)- (+)-N, N-Dimethyl-3-(naphthalen-l-yloxy)-l- phenylpropan-1 -amine tartrate is of purity ranging from about 15% to about 5%. The (S)- (+)-N,N-Dimethyl-3-(Naphthalen-l-yloxy)-l-phenylpropan-l -amine is optionally converted to its pharmaceutically acceptable salt, preferably hydrochloride salt.

The method yields chemically and enantiomerically pure (+)-- Dapoxetine hydrochloride. The (+)- Dapoxetine hydrochloride enantiomeric purity 99.0 -99.9%. (S)-N,N-Dimethyl-3-(Naphthalen-1-yloxy)-1-Phenylpropan-1 -Amine

1-(3-chloro-3-phenylpropoxy)naphthalene

3-(naphthalen-1 -yloxy)-1 -phenylpropan-1 -ol

(II)

(I)

H₃C....CH₃ C₂H₇N

N Mol. Wt.: 45.08

loxy)-1 -

(S)-

phenylpropan-1-amine. Tartarate

(IV)

NaOH

- 1 -

(S)-/V,A/-di

(V) (VI)

The embodiments of the present invention encompasses the modifications as applicable by a person skilled in the art to achieve the object of the present invention, and hence the present invention is not restricted to the disclosure herein by description and examples.

The present disclosure is now described with reference to the following examples. However, as aforementioned it should not be construed that the disclosure is limited thereto. EXAMPLES:

A. Process for preparation of l-(3-Chloro-3-phenylpropoxy)-Naphtha ene

Example- 1

3-(Naphthalene-l-yloxy)-l-phenylpropan-l-ol (50g; 0.179mol) is dissolved in Dichloromethane (250 ml). The mixture is cooled to 0-5°C, thionyl chloride (26.0 g; 0.215 mol) is added over a period of three hours followed by 0.5 ml DMF. The resulting mixture is concentrated to dryness and diluted with mixture of water (100ml) and Dichloromethane.(100 ml). Organic layer is distilled to get l-(3-Chloro-3-phnylpropoxy)-naphthalene (54 g; Yield 98%)

GCMs m/z Calc. C₁₉Hi₇C10 ; 296.7 Found 296.0 HPLC Purity; 96.0%

Example-2

3-(Naphthalene-l-yloxy)-l-phenylpropane-l-ol (50g; 0.179mol) is dissolved in Dichloromethane (250 ml). The mixture is cooled to 0-5°C, thionyl chloride (26.0 g; 0.215 mol)is added over a period of three hours followed by 0.5 ml DMF. The reaction is diluted with water (100 ml). The separated organic layer is distilled off completely to get l-(3-Chloro-3-phenylpropoxy)- naphthalene (50 g; Yield 93%)

HPLC Purity; 96.9%

B. Preparation of S -(+)-N,N-Dimethyl-3-(Naphthalen-l-yloxy)-l-phenylpropan-l-ainine Tartrate. Example 3 : l-(3-Chloro-3-phenylpropoxy)-naphthalene (50 g; 0.168 mol) is added to aqueous solution of dimethylamine (400 ml) followed by triethylamine (50 g).The reaction mixture is stirred at 25- 30°C for 30 hr. Organic layer is separated after completion of reaction and is treated with dil HC1 (100 ml). Separated aqueous layer is extracted with dichlomethane after adjusting pH to 10-12 by caustic solution. The organic layer is concentrated to get thick viscous mass which is dissolved with acetonitrile (200 ml), and D-(-)-Tartaric acid (11.8 g 0.078 mol) dissolved in water (18 ml) separately is added to reaction mass at 25-30 °C. The precipitate is stirred for 2 hr at 25-30°C, filtered and washed with acetonitrile (50 ml). The solid is dried, yield 16 g.

HPLC purity; 99% HPLC, Chiral purity; (S-Isomer; 95%) (R-Isomer; 5%) [a] a ²⁵ (C= 1 , MeOH) = (+ ) 65° MR: 115-117°C Example-4: l-(3-Chloro-3-phenylpropoxy)-naphthalene (50 g; 0.168 mol) is added to dimethylamine (400 ml), THF (100 ml) followed by triethylamine (50 ml). The reaction mass is stirred to 15-30°C for 30-40 hr. Organic layer is separated and washed with water. Separated organic layer is treated with dil HC1 (500 ml) and organic layer is discarded. To the aqueous layer, sodium hydroxide solution is added to adjust the pH to 9-10 and extracted with Dichloromethane; it is concentrated completely to dryness to get thick residue. To this mass, is added Ethanol (500 ml), L-(+)~Tartaric acid (24.60 g 0.163 mol) and water (35 ml).The reaction mixture is stirred at 25- 30 °C for 3 hr and cooled to 0-5°C.It is filtered and re purified by ethanol(250 ml). The dry weight obtained is 14 g.

[a] D ²⁵ (C=l, MeOH) = (+ ) 88.58° MR; 115-117°C

HPLC; Chiral (S-Isomer 95%; R-Isomer-5%)

C.Preparation of ^S')-(+)-N,N-Dimethyl-3-(naphthalen-l-yloxy)-l-phenylpropan-l-amine Hydrochloride

Example-5 (S)- (+)-N,N-Dimethyl-3-(Naphthalen-l-yloxy)-l-phenylpropan-l -amine Tartrate (15 g ) is charged in a mixture of water (90 ml) and dichloromethane (90 ml). Organic layer is separated after adjustment of pH 9-10 by 5 % caustic solution. Organic layer is distilled to dryness and is dissolved in ethylacetate (40 ml). To clear a solution; IPA -HC1 (4.0 ml) is added at 25-30 °C, stirred for 3 hr and filtered at 0-5°C, washed with chilled ethylacetate (20 ml). The solid mass is dried, yield 6.5 g.

[a] D ²⁵ (C=l, MeOH) = (+ ) 130°

HPLC Chiral (S-Isomer 99.90, R-Isomer 0.08)

HPLC Purity; 99.91% MR; 182-183°c

ExampIe-6

The solid, (5^-(+)-N,N-Dimethyl-3-(Naphthalen-l-yloxy)-l-phenylpropan-l -amine Tartrate (12.0 g) is added into a mixture of dichloromethane (75ml) and water (75 ml). The organic layer separated after adjusting pH to 8-10. The organic layer is distilled completely to dryness to obtain a thick mass of solid.

[a] D ²⁵ (C=l, MeOH) = (+ ) 104°

HPLC; Chiral (S-Isomer; 95%; R-Isomer-5%)

To the above thick mass IPA-HCl (3 ml) is added in presence of ethyl acetate (30 ml). It is stirred for 2 hr at 25-30°C. The solid is filtered at 0-5°C.Yield is 10 gm.

[a] D ²⁵ (C=l, MeOH) = (+ ) 128°

HPLC Chiral (S-Isomer 99.80, R-Isomer 0.08)

HPLC Purity; 99.81%

MR; 182-183°C Example-7

Solution of (S)- (+)-N,N-Dimethyl-3-(Naphthalen-l-yloxy)-l-phenylpropan-l-amine (6 gm) in ethyl acetate (30 ml) is stirred at 25-30°C for one hr followed by addition of IPA-HCl ( 4-5 ml). The precipitate mass is stirred at 0-5 °C for one hr. It is filtered, washed with chilled ethyl acetate (6 ml) and dried. Dry weight; 5 gm. [a] D ²⁵ (C= 1 , MeOH) = (+ ) 129^°

HPLC Chiral (S-Isomer 99.90, R-Isomer 0.09)

HPLC Purity; 99.92%

MR; 181-183 C

D. Preparation of N, N-Dimethyl-3-(naphtha en-l-yloxy)-l-phenylpropan-l-amine

ExampIe-8 l-(3-Chloro-3-phenylpropoxy)-naphthalene (50g 0.168 mol) is added to aqueous Dimethyl amine solution (400 ml) at 25-30°C followed by triethyl amine (50.0 ml). The reaction mixture is stirred for 30 hr at 25-30°C. The progress of reaction is monitored by TLC. A mixture of toluene (250ml) and water (250 ml)is added and acidified with HCl. The aqueous solution is basified with NaOH solution and extracted with Dichloromethane (150 ml). Organic layer is distilled to get N, N-Dimethyl-3-(Naphthalen-l-yloxy)-l-phenylpropan-l-amine (40 g, 77%)

'H NMR (CDCI3) δ 7.99-7.99(d,lH), δ 7.76-7.78 (d,lH), δ 7.57-7.59 (t,2H), δ 7.38-7.50 (m, 6H), δ 7.24-7.28 (q, 1H), δ 4.14-4.18 (m, 1H), δ 3.72-3.78 (m, 1H), δ 3.07-3.15 (m,lH), δ 2.92- 2.93(s, 3H), δ 2.80-2.88 (m, 1H), δ 2.63-2.62 (s, 3H) HPLC Purity: 96%

Example-9

A solution of l-(3-Chloro-3-phenylpropoxy)-naphthalene (50 g 0.168 mol) and THF (300 ml) is cooled to 0-5°C. To the above reaction mass Dimethyl amine gas is purged for 5 hr, followed by TBAB (0.5gm) and it is maintained for 40 hr at 25- 30°C. The progress of reaction is monitored by TLC. A mixture of toluene (250 ml) and water (250 ml) is added and acidified with HCl. The aqueous layer is basified with NaOH solution and extracted with Dichloromethane (150 ml). Organic layer is distilled completely to get N,N-Dimethyl-3-(Naphthalen-l-yloxy)-l- phenylpropan-1 -amine (30 g, 60%)

D. Preparation of (S)- (+ -N,N-Dimethyl-3-(naphtha en-l-vIoxy)-l-phenylpropan-l-amine Tartarate

Example- 10

A solution of D-(-)-Tartaric acid 7.37 g (0.049 mol) in 20 ml of water is added to a separate solution of N,N-Dimethyl-3-(naphthalen-l-yloxy)-l-phenylpropan-l -amine (25 g, 0.0818 mol) in acetonitrile (125ml)and stirred for 2 hr at 25-30 °C. It is chilled to 0-5 °C for 1 hr. Solid is filtered and washed with acetonitrile 25 ml and dried (17 g).

[a] D ²⁵ (C= 1 , MeOH) = (+ ) 60^°

HPLC; Chiral (S-Isomer 85%; R-Isomer 15%)

MP. 115-117 °C Example- 11

A solution of D-(-)-Tartaric acid 24.57 g (0.1637mol) in 70 ml of water is added to a solution of N,N-Dimethyl-3-(naphthalen-l-yloxy)-l-phenylpropan-l -amine 50 g(0.1637 mol) in acetonitrile 250ml is stirred for 2 hr at 25-30 °C. It is chilled at 0-5 °C for 1 hr. Solid is filtered and washed with acetonitrile 50 ml and dried(32 g).

[a] D ²⁵ (C=l, MeOH)— (+ ) 65°

HPLC; Chiral (S-Isomer 90 %; R-Isomer 10 %)

E. Preparation of (S)- (+VN,N-Dimethyl-3-(Naphthalen-l-yloxy)-l-phenylpropan-l-amine

Example- 12 (S)- (+)-N,N-Dimethyl-3-(naphthalen-l-yloxy)-l-phenylpropan-l -amine Tartrate (15 g) is added to a mixture of dichloromethane (75ml) and water (75 ml) each. The pH of reaction mixture is adjusted to 8-9 with NaOH solution. Organic layer is separated and concentrated to dryness to get (S)- (+)-N,N-Dimethyl-3-(naphthalen-l-yloxy)-l-phenylpropan-l -amine; Yield 7 gm.

[a] D ²⁵ (C= 1 , MeOH) = (+ ) 102°

HPLC Chiral ( S-Isomer 95.13, R-Isomer-4.8%)

Claims

WE CLAIM

1. A method for preparing (S)- (+)-N, N-Dimethyl-3 -(Naphthalen-1 -yloxy)- 1-phenylpropan-

1 -amine or to its pharmaceutically acceptable salt, said method comprising acts of

a. preparing compound of formula I from 3 -(N aphthalene- 1 -yloxy)- 1 -phenylpropane- 1 -ol;

X= CI or Br

Formula I b. preparing (S)- (+)-N, N-Dimethyl-3-(naphthalen-l -yloxy)- 1-phenylpropan-l -amine tartrate from the compound of formula I;

c. reacting the (S)- (+)-N,N-Dimethyl-3-(naphthalen-l -yloxy)- 1-phenylpropan-l -amine tartrate with base to obtain the (S)- (+)-N,N-Dimethyl-3-(naphthalen-l -yloxy)- 1-phenylpropan- 1 -amine; and

d. optionally converting the (S)- (+)-N,N-Dimethyl-3-(naphthalen-l -yloxy)- 1- phenylpropan-1 -amine to its pharmaceutically acceptable salt.

2. The method as claimed in claim 1, wherein the compound of formula I is prepared using halogenating reagent selected from a group comprising thionyl chloride, phosphorus trichloride, phosphorus pentachloride, zinc chloride in hydrochloric acid, thionyl bromide and mixture thereof.

3. The method as claimed in claim 1, wherein the (S)- (+)-N, N-Dimethyl-3-(Naphthalen-l- yloxy)- 1-phenylpropan-l -amine tartrate is prepared by a method comprising acts of,

a. reacting the compound of formula I with dimethyl amine to obtain the N,N-Dimethyl-3- (naphthalen-1 -yloxy)- 1-phenylpropan-l -amine; and

b. treating the N,N-Dimethyl-3 -(naphthalen-1 -yloxy)- 1-phenylpropan-l -amine with Tartaric acid to obtain the (S)- (+)-N, N-Dimethyl-3 -(naphthalen-1 -yloxy)- 1-phenylpropan-l - amine tartrate.

4. The method as claimed in claim 3, wherein the tartaric acid is selected from a group comprising Z(+)-tartaric acid and D(-)-tartaric acid.

5. The method as claimed in claim 1, wherein the base is selected from a group comprising sodium hydroxide, potassium hydroxide, potassium t- butoxide, strontium hydroxide, calcium hydroxide, barium hydroxide and mixture thereof.

6. The method as claimed in claim 1, wherein the (S)- (+)-N,N-Dimethyl-3-(naphthalen-l- yloxy)-l-phenylpropan-l -amine is converted to its pharmaceutically acceptable salt using acid selected from a group comprising hydrochloric acid and hydrobromic acid.

7. The method as claimed in claim 6, wherein the pharmaceutically acceptable salt of (S)- (+)-N,N-Dimethyl-3-(naphthalen-l-yloxy)-l-phenylpropan-l -amine is of hydrochloric acid.

8. The method as claimed in claim 1, wherein the prepared (S)- (+)-N, N-Dimethyl-3- (naphthalen-l-yloxy)-l-phenylpropan-l -amine tartrate is of purity ranging from about 85% to about 95%.

9. The method as claimed in claim 1, wherein the prepared (S)- (+)-N, N-Dimethyl-3- (naphthalen-l-yloxy)-l-phenylpropan-l -amine hydrochloride is of purity ranging from about 99% to about 99.9%.

10. A compound of formula I,

Wherein X=C1 or Br

Formula -I

11. The compound as claimed in claim 10 compound of formula I is

12. A method for preparing compound of formula I, comprising act of reacting 3- (Naphthalene-l-yloxy)-l-phenylpropane-l-ol with halogenating agent.

13. The method as claimed in claim 12, wherein the halogenating agent is selected from a group comprising thionyl chloride, thionyl bromide, phosphorus trichloride, phosphorus pentachloride, zinc chloride in hydrochloric acid and mixture thereof.

14. The method as claimed in claim 12, wherein the halogenating agent is thionyl chloride.

15. The method as claimed in claim 12, wherein the reaction is carried out at a temperature ranging from about 0°C to about 10°C, preferably from about 0°C to about 5°C.

16. A method for preparing (S)- (+)-N, N-Dimethyl-3-(Naphthalen- 1 -yloxy)- 1 -phenylpropan- 1 -amine or its salt from formula I, said method comprising acts of

a. converting the compound of formula I to (S)- (+)-N, N-DimethyI-3-(Naphthalen-l- yloxy)- 1 -phenylpropan- 1 -amine tartrate;

Wherein X= CI or Br

Formula I

b. reacting the (S)- (+)-N,N-Dimethyl-3-(Naphthalen-l -yloxy)- 1 -phenylpropan- 1 -amine tartrate with base to obtain (S)- (+)-N,N-Dimethyl-3-(Naphthalen-l -yloxy)- 1 -phenylpropan- 1- amine; and

c. optionally converting X e(S)- (+)-N,N-Dimethyl-3-(Naphthalen-l-yloxy)-l- phenylpropan-1 -amine to its salt.

17. The method as claimed in claim 16, wherein the (S)- (+)-N, N-Dimethyl-3-(Naphthalen- 1 -yloxy)- 1 -phenylpropan- 1 -amine tartrate is prepared by a method comprising acts of, a. reacting the compound of formula I with dimethyl amine to obtain the N,N-Dimethyl-3- (naphthalen- 1 -yloxy)- 1 -phenylpropan- 1 -amine; and b. treating the N,N-Dimethyl-3-(naphthalen-l-yloxy)-l-phenylpropan-l -amine with Tartaric acid to obtain the (S)- (+)- N, N-Dimethyl-3-(naphthalen-l-yloxy)-l-phenylpropan-l- amine tartrate.

18. The method as claimed in claim 17, wherein the tartaric acid is selected from a group comprising L(+)~ tartaric acid and D(-)-tartaric acid.

19. The method as claimed in claim 16, wherein the (S)- (+)-N,N-Dimethyl-3-(naphthalen-l- yloxy)-l-phenylpropan-l -amine is converted to its salt using acid selected from a group comprising hydrochloric acid and hydrobromic acid.

20. The method as claimed in claim 16, wherein the salt of (S)- (+)-N,N-Dimethyl-3- (naphthalen-l-yloxy)-l-phenylpropan-l -amine is salt of hydrochloric acid.

21. The method as claimed in claim 16, wherein the prepared (S)- (+)-N, N-Dimethyl-3- (naphthalen-l-yloxy)-l-phenylpropan-l -amine tartrate is of purity ranging from about 85% to about 95%.

22. The method as claimed in claim 16, wherein the prepared (S)- (+)-N, N-Dimethyl-3- (naphthalen-l-yloxy)-l-phenylpropan-l -amine hydrochloride is of purity ranging from about 99% to about 99.9%.